We developed a high-throughput approach to knockout (KO) and phenotype mouse orthologs of the 5,000 potential drug targets in the human genome. As part of the phenotypic screen, dual-energy X-ray absorptiometry (DXA) technology estimates body-fat stores in eight KO and four wild-type (WT) littermate chow-fed mice from each line. Normalized % body fat (nBF) (mean KO % body fat/mean WT littermate % body fat) values from the first 2322 lines with viable KO mice at 14 weeks of age showed a normal distribution. We chose to determine how well this screen identifies body-fat phenotypes by selecting 13 of these 2322 KO lines to serve as benchmarks based on their published lean or obese phenotype on a chow diet. The nBF values for the eight benchmark KO lines with a lean phenotype were ≥1 s.d. below the mean for seven (perilipin, SCD1, CB1, MCH1R, PTP1B, GPAT1, PIP5K2B) but close to the mean for NPY Y4R. The nBF values for the five benchmark KO lines with an obese phenotype were >2 s.d. above the mean for four (MC4R, MC3R, BRS3, translin) but close to the mean for 5HT2cR. This screen also identifies novel body-fat phenotypes as exemplified by the obese kinase suppressor of ras 2 (KSR2) KO mice. These body-fat phenotypes were confirmed upon studying additional cohorts of mice for KSR2 and all 13 benchmark KO lines. This simple and cost-effective screen appears capable of identifying genes with a role in regulating mammalian body fat.

What is the best way to arrange dams within river basins to benefit society? Recent interest in this question has grown in response to the worldwide trend toward developing hydropower as a source of renewable energy in Asia and South America, and the movement toward removing

In 1998, Burago–Kleiner and McMullen independently proved the existence of separated nets in double-struckRd which are not bi‐Lipschitz equivalent (BL) to a lattice. A finer equivalence relation than BL is bounded displacement (BD). Separated nets arise naturally as return times to a section for minimal double-struckRd‐actions. We analyze the separated nets which arise via these constructions, focusing particularly on nets arising from linear double-struckRd‐actions on tori. We show that generically these nets are BL to a lattice, and for some choices of dimensions and sections, they are generically BD to a lattice. We also show the existence of such nets which are not BD to a lattice.

Kinetics and bioavailability offlucytosine were studied in 5 subjects with normal renalfunction.